N-acetyl-L-cysteine (NAC) was initially introduced as a treatment for mucus reduction and widely used for chronic respiratory conditions associated with mucus overproduction. However, the mechanism of action for NAC extends beyond its mucolytic activity and is complex and multifaceted. Contrary to other mucoactive drugs, NAC has been found to exhibit antioxidant, anti-infective, and anti-inflammatory activity in pre-clinical and clinical reports. These properties have sparked interest in its potential for treating chronic lung diseases, including chronic obstructive pulmonary disease (COPD), bronchiectasis (BE), cystic fibrosis (CF), and idiopathic pulmonary fibrosis (IPF), which are associated with oxidative stress, increased levels of glutathione and inflammation. NAC’s anti-inflammatory activity is noteworthy, and it is not solely secondary to its antioxidant capabilities. In ex vivo models of COPD exacerbation, the anti-inflammatory effects have been observed even at very low doses, especially with prolonged treatment. The mechanism involves the inhibition of the activation of NF-kB and neurokinin A production, resulting in a reduction in interleukin-6 production, a cytokine abundantly present in the sputum and breath condensate of patients with COPD and correlates with the number of exacerbations. The unique combination of mucolytic, antioxidant, anti-infective, and anti-inflammatory properties positions NAC as a safe, cost-effective, and efficacious therapy for a plethora of respiratory conditions.

Which patients should be monitored for coinfections or should receive empirical antibiotic treatment, in patients with an acute viral respiratory infection, is largely unknown. We evaluated the prevalence, characteristics, outcomes of coinfected patients, and risk factors associated with a coinfection among patients with an acute viral infection. A retrospective, single-center study recruited consecutive patients from October 2022 to March 2023 presenting to the emergency department with signs of a respiratory tract infection. Patients were screened for respiratory viruses and bacterial/fungal secondary infections according to local standard procedures. Outcomes included severe disease, in-hospital complications, all-cause in-hospital and ICU-related mortality, time to death, time to discharge, and time to coinfection. The analysis included 652 patients. A viral infection and a secondary bacterial/fungal infection were detected in 39.1% and 40% of cases. Compared with the rest of the cohort, coinfected patients had more frequently severe disease (88.3%, p < 0.001; 51% in patients with SARS-CoV-2) and higher in-hospital mortality (16.5%, p = 0.010). Nephropathy (OR 3.649, p = 0.007), absence of COVID-19 vaccination (OR 0.160, p < 0.001), SARS-CoV-2 infection (OR 2.390, p = 0.017), and lower blood pressure at admission (OR 0.980, p = 0.007) were independent risk factors for coinfection. Multidrug-resistant pathogens were detected in 30.8% of all coinfections. Patients with a viral infection are at high risk of bacterial coinfections, which carry a significant morbidity and mortality burden.

Acute respiratory failure (ARF) is a common life-threatening medical condition, with multiple underlying etiologies. In these cases, many factors related to systemic inflammation, prolonged use of steroids, and lung mechanical abnormalities (such as hyperinflation or increased elastic recoil due to pulmonary oedema or fibrosis) may act as synergic mechanisms leading to diaphragm dysfunction. The assessment of diaphragm function with ultrasound has been increasingly investigated in the emergency department and during hospital stay as a valuable tool for providing additional anatomical and functional information in many acute respiratory diseases. The diaphragmatic ultrasound is a noninvasive and repeatable bedside tool, has no contraindications, and allows the physician to rapidly assess the presence of diaphragmatic dysfunction; this evaluation may help in estimating the need for mechanical ventilation (and the risk of weaning failure), as well as the risk of longer hospital stay and higher mortality rate. This study presents an overview of the recent evidence regarding the evaluation of diaphragmatic function with bedside ultrasound and its clinical applications, including a discussion of real-life clinical cases.

Artificial intelligence (AI) can make intelligent decisions in a manner akin to that of the human mind. AI has the potential to improve clinical workflow, diagnosis, and prognosis, especially in radiology. Acute respiratory distress syndrome (ARDS) is a very diverse illness that is characterized by interstitial opacities, mostly in the dependent areas, decreased lung aeration with alveolar collapse, and inflammatory lung edema resulting in elevated lung weight. As a result, lung imaging is a crucial tool for evaluating the mechanical and morphological traits of ARDS patients. Compared to traditional chest radiography, sensitivity and specificity of lung computed tomography (CT) and ultrasound are higher. The state of the art in the application of AI is summarized in this narrative review which focuses on CT and ultrasound techniques in patients with ARDS. A total of eighteen items were retrieved. The primary goals of using AI for lung imaging were to evaluate the risk of developing ARDS, the measurement of alveolar recruitment, potential alternative diagnoses, and outcome. While the physician must still be present to guarantee a high standard of examination, AI could help the clinical team provide the best care possible.

Respiratory viral infections trigger immune and inflammatory responses that can be associated with excessive oxidative stress, glutathione (GSH) depletion, and a cytokine storm that drives virus-induced cell/tissue damage and severe disease. Erdosteine is a thiol-based drug with proven mucolytic, anti-inflammatory, antioxidant, and antibacterial properties, but less is known about its antiviral effects. We performed in vitro studies to investigate the antiviral and anti-inflammatory activity of erdosteine in A549-hACE2 human lung epithelial cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or respiratory syncytial virus (RSV) and in Caco-2 human colon carcinoma cells infected with influenza A virus (H1N1). The cells were treated with different concentrations of erdosteine or its active metabolite 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MET-1) before and after viral infection. The viral replication/load in the cell culture supernatants was measured by real-time quantitative polymerase chain reaction (RT-qPCR) assay and digital droplet PCR. The gene expression of innate immune response signaling pathways and oxidative stress was analyzed by reverse transcription PCR custom-array. The results showed that erdosteine and its active metabolite, at concentrations consistent with an approved therapeutic human dosage, were not directly cytotoxic and had significant antiviral effects in cells pre-infected with SARS-CoV-2, RSV, and H1N1. The transcriptome analysis showed that erdosteine activated innate immune responses by stimulating overexpression of type I interferon and inflammasome pathways and modulated oxidative stress by inducing the modulation of oxidative stress and GSH pathways. These findings suggest that erdosteine may be a useful treatment for respiratory viral infections.

It is not known if the degrees of improvement in oxygenation obtained by CPAP can predict clinical outcomes in patients with COVID-19 pneumonia. This was a retrospective study conducted on patients with severe COVID-19 pneumonia treated with CPAP in three University hospitals in Milan, Italy, from March 2020 to March 2021. Arterial gas analysis was obtained before and 1 h after starting CPAP. CPAP failure included either death in the respiratory units while on CPAP or the need for intubation. Two hundred and eleven patients (mean age 64 years, 74% males) were included. Baseline median PaO₂, PaO₂/FiO₂ ratio (P/F), and the alveolar-arterial (A-a) O₂ gradient were 68 (57–83) mmHg, 129 (91–179) mmHg and 310 (177–559) mmHg, respectively. Forty-two (19.9%) patients died in the respiratory units and 51 (24.2%) were intubated. After starting CPAP, PaO₂/FiO₂ increased by 57 (12–113; p < 0.001) mmHg, and (A-a) O₂ was reduced by 68 (−25–250; p < 0.001) mmHg. A substantial overlap of PaO₂, P/F, and A-a gradient at baseline and during CPAP was observed in CPAP failures and successes; CPAP-associated improvements in oxygenation in both groups were similar. In conclusion, CPAP-associated improvements in oxygenation do not predict clinical outcomes in patients with severe COVID-19 pneumonia.